3-Chloropropionyl chloride → N-[(R)-1-(5-bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-3-chloro-N-(4-methoxy-benzyl)-propionamide

Participants

Reaction Steps

A suspension of [(R)-1-(5-bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-(4-methoxy-benzyl)-amine (7.98 g, 16.5 mmol) in a mixture of chloroform (52 ml) and saturated sodium hydrogen carbonate solution (78 ml) was treated dropwise at 0° C. with 3-chloropropanoyl chloride (2.57 g, 19.8 mmol). The reaction mixture was left to warm to room temperature and vigorous stirring continued for 16 hours. For the workup, the layers were separated, the aqueous layer extracted with chloroform (100 ml), thereupon, the combined organic layers dried over sodium sulfate and evaporated at reduced pressure. After chromatography on Silicycle-Si-amine column using a gradient of heptane and ethyl acetate=100/0 to 60/10 as the eluent, besides recovery of 57% of the starting material, N-[(R)-1-(5-bromo-2-fluoro-phenyl)-2-(tert-butyl-dimethyl-silanyloxy)-1-methyl-ethyl]-3-chloro-N-(4-methoxy-benzyl)-propionamide (intermediate C9A) was obtained as a colourless viscous oil (2.08 g, 22% of theory). MS (ISP): m/z=536.2, 538.3 [M−Cl+H]+.

Provenance & Evidence